Background: Adolescent HIV and AIDS are now primarily attributable to risky sexual behaviors or substance use. Infection rates are high among homeless youth who have additional risk factors, such as survival sex or multiple partners. Aims: 1) The Larkin Street Youth Center (LSYC)- University of California, San Francisco (UCSF) collaborative will recruit, enroll, and maintain a cohort of 75 HIV+ street involved youth into the San Francisco Adolescent Medicine Trials Unit (AMTU) to provide them with access to behavioral and clinical HIV research; 2) The LSYC-UCSF collaborative will recruit, enroll, and maintain a cohort of 125 HIV negative but at-risk street involved youth into the San Francisco AMTU to provide them with access to on primary prevention of HIV and clinical studies; 3) The LSYC-UCSF collaborative will continue to expand enrollment of HIV + youth of color in San Francisco. Contribution to the ATN: LSYC in San Francisco has provided comprehensive services to runaway and street youth for seventeen years, and comprehensive care to HIV + youth since 1990. Since 1998, LSYC, the UCSF Division of Adolescent Medicine, and the UCSF Pediatric AIDS program have collaborated in a Title IV funded center for the care of HIV+ youth. The Larkin Street Aftercare and Assisted Care (ACAC) program provides comprehensive medical care, housing, case management, and social support services to HIV+ youth at a single site in San Francisco. LSYC has a history of successful collaborative longitudinal research of street youth. Approach: The ACAC program provided comprehensive services to 82 HIV+ street-involved clients in FY 98/99. All but one were infected through high risk sexual behaviors or substance. Youth are identified through an extensive outreach program, which has increased outreached and HIV-testing by minority youth. 216 youth have been tested in the first 8 months of FY99/00, with a 6% rate of seropositivity. LSYC also provides a continuum of services to over two thousand HIV-negative but at-risk youth every year, over 400 of whom receive medical care at the LSYC clinic. Investigators: The Principal investigator, co-investigators, and project coordinator have extensive experience in multi-site collaborative research, cohort-based research, research with street youth, adolescent medicine, and HIV primary care. Innovation/Environment: LSYC has been a model in care of hard-to-reach populations. LSYC offers a complete continuum of services for HIV + and at risk homeless youth which are provided in a youth friendly environment.